This research effort is a long-term commitment to develop intratumoral drug delivery as a local chemotherapy to supplement twnor thermoablation for the treatment of liver cancers. In this treatment, image-guided thermoablation first destroys the majority of the tumor tissue by heat. The drug delivery device, in the shape of a cylindrical millirod, is then implanted into the thermoablated tumors to kill any cancer cells remaining after thermoablation. The objective of the proposed application is to develop and evaluate drug delivery systems that can modulate the release of doxorubicin, an anticancer drug, for intratumoral drug delivery to thermoablated tumor tissues. The central hypothesis is that polymer millirods with dual release kinetics-an initial burst release followed by a sustained release of drugs-can provide the maximal therapeutic effect to supplement thermoablation in the treatment of liver tumors. To test this central hypothesis, we will carry out the following four specific aims: (1) rational design of polymer millirods with dual release kinetics by mathematical models; (2) development and characterization of polymer millirods with dual release kinetics; (3) pharmacokinetic analysis of implanted polymer millirods in rabbit VX-2 liver tumors; (4) validation of drug efficacy by monitoring of tumor size and histology analysis. Successful execution of the proposed application will establish a solid pharmacological basis and bioengineering foundation for the development of drug delivery systems for intratumoral drug delivery. In combination with image-guided thermoablation, this therapeutic procedure should provide an innovative, minimally invasive and less toxic therapy for the treatment of liver tumors.